Papilloma Viruses and Retroviruses

Question 1

In which cells do human papillomaviruses replicate?

Answer 1

Stratified epithelium

Question 2

What are the two early papillomavirus proteins that are crucial in subsequent cellular regulation steps?

Answer 2

E1 and E2

Question 3

What do papillomavirus proteins E1 and E2 do?

Answer 3

They recruit replication machinery to the origin of replication.

Question 4

Which HPV protein sequesters Rb?

Answer 4

E7

Question 5

Which HPV protein degrades p53?

Answer 5

E6

Question 6

What event initiates late gene expression in HPV-infected cells? Name two late genes and state what they are.

Answer 6

Keratinocyte differentiation. L1 and L2 are capsid proteins.

Question 7

Which two HPV strains cause cervical cancer?

Answer 7

16 and 18

Question 8

How does HPV 16/18 transformation in cervical epithelial cells work?

Answer 8

1. The viral genome is integrated into the cell’s DNA.
2. E6 and E7-containing cells are selected for.
3. Cell cycle is driven without functional p53 and Rb –> malignancy

Question 9

Do HPV-infected cells with E2 become malignant?

Answer 9

No, E2 “turns down the process.”

-don’t know how

Question 10

What is the defining feature of a retrovirus?

Answer 10

They replicate through a DNA intermediate called a provirus that is integrated into the host genome.

Question 11

What is it called when a retrovirus integrates into germline DNA and is inherited by offspring?

Answer 11

Endogenous virus.

Question 12

Describe the retroviral genome.

Answer 12

SS (+) RNA with 5’ cap and poly-A tail.

Question 13

Name four genes that retroviruses encode.

Answer 13

1. pro (protease)
2. pol (reverse transcriptase and integrase)
3. gag (internal proteins)
4. env (envelope proteins)

Question 14

What happens after a retrovirus penetrates a host cell?

Answer 14

Genome is released into cytoplasm, then dsDNA is synthesized and integrase integrates it into the host chromosome.

Question 15

Briefly describe retroviral DNA synthesis.

Answer 15

1. Using a tRNA primer, reverse transcriptase copies a short segment at the 5’ end of the (-) RNA viral genome.
2. The newly synthesized copy + tRNA primer jumps to a matching sequence on the 3’ end of the viral genome and copies the strand.
3. Reverse transcriptase jumps back to the parent strand to copy the U5 segment to the 3’ end. Result is a double-stranded sequence with LTR ends that can insert into the host genome.

Question 16

What are the two ways in which a retrovirus can cause cancer?

Answer 16

1. LTR insertion next to a proto-oncogene in the host cell chromosome (similar to Burkitt’s lymphoma - myc is put right next to an antibody gene and is overexpressed).
2. Transduction event puts the cell’s proto-oncogene into the viral genome.